In recent years the incidence of hepatocellular carcinoma (HCC) has increased substantially in Japan. Data from Japan and some European countries suggest that HCCs there may be associated frequently with the hepatitis C virus (HCV). In contrast to Japanese who live in Japan, the descendants of Japanese immigrants to Hawaii have not experienced a substantial increase in the incidence of HCC in recent years. To evaluate the roles of HBV and HCV among HCC patients in Hawaii and to compare the results to published reports of HCC patients in Japan, a cohort of 5924 Japanese-American men were examined between 1967 to 1970. By 1992, 24 incident cases of hepatocellular carcinoma (HCC) were histologically confirmed in this group of men. Hepatitis B surface antigen was detected in 15/24 (62%) HCC cases compared with 2/72 (3%) controls (odds ratio, 58.3; 95% confidence interval, 10.0-205.5). None of the cases and only one of the controls had antibody to the hepatitis C virus. This study demonstrates a strong association of hepatocellular carcinoma with hepatitis B virus infection, but not with hepatitis C virus infection among patients of Japanese ancestry in Hawaii.